1. Field of the Invention
The invention relates to chemical compositions and methods for using the compositions for simultaneously cleaning and decontaminating devices.
2. Description of Related Art
A variety of industries require that devices used within the industry be cleaned and decontaminated. Examples of two such sectors are the brewing industry and the medical arena. Such sectors require efficient and effective device cleaning and decontaminating foremost for health and safety reasons, but also for economic reasons.
Within the medical field, a variety of devices exist to serve important medical functions. Medical devices may be single-use or may be reusable. Cleaning and decontaminating products for medical devices may also be single-use or reusable and their associated methods or processes of application may be applied once or repeated. As used herein, decontamination is the removal of hazardous or unwanted materials such as bacteria, mold spores or other pathogenic life forms and the like, wherein high- and intermediate-level disinfection and sterilization represent different levels of decontamination. The time interval for achieving decontamination herein for medical devices other than kidney dialyzers is 30 minutes or less. No limitation is placed on the decontamination time useful for kidney dialyzers. These time intervals pertain to the time required to decontaminate a single medical device and do not apply to solution reuse time periods. Sterilization is a level of decontamination representing the complete elimination or destruction of all forms of microbial life, including fungal and bacterial spores. High-level disinfection is a level of decontamination representing a process that eliminates many or all pathogenic microorganisms, with the exception of bacterial spores, from inanimate objects.
Regulatory agencies and other groups have classified medical devices, processes, and cleaning and decontaminating products according to basic principles related to infection control. Medical devices are classified as critical, semicritical or noncritical. Critical devices, for example, scalpels, needles and other surgical instruments, enter sterile tissues or the vascular system. Such devices require sterilization with a process or with prolonged contact with a sporicidal chemical prior to reuse.
Semicritical devices, for example, flexible endoscopes, bronchoscopes, laryngoscopes, endotracheal tubes and other similar instruments, touch all mucous membranes except dental mucous membranes. Such devices require high-level disinfection with a process or short contact with a sporicidal chemical prior to reuse. High-level disinfection can be expected to destroy all microorganisms with the exception of high numbers of bacterial spores. An FDA regulatory requirement for high- and intermediate-level disinfectants is 100% kill of 1,000,000 organisms of Mycobacterium tuberculosis (M. tuberculosis) in the presence of 2% horse serum in a quantitative tuberculocidal test. This is a suspension test following the EPA Guidelines for the Quantitative Tuberculocidal Procedure. An additional FDA regulatory requirement for high-level disinfectants is that they must also achieve sterilization over a longer exposure time than the disinfection regimen time, as long as sterilization is achieved with 20 hours. The ability to achieve sterilization is measured by sporicidal activity as determined by the AOAC Sporicidal Test, AOAC Official Methods of Analysis, 15th edition, 1995. This test measures the ability of a solution to sterilize surfaces contaminated with dried bacterial spores. Spores of Bacillus subtilis ATCC #19659 and/or Clostridium sporogenes ATCC #3584 are used for this test. Common commercially available high-level disinfectants include glutaraldehyde solutions between 2.4-3.4%w/v which also typically require activation with an alkaline buffer just prior to use. Also available are an acidic (pH 1.60-2.00) hydrogen peroxide (H2O2) formulation comprising 7.5%w/v hydrogen peroxide and another antimicrobial agent (for example, Sporox(copyright), Reckitt and Colman, Inc.), and an acidic mixture of 1.0%w/v H2O2 and 0.08%w/v peracetic acid (PAA) (Peract(trademark) 20, Minntech Corp. or Cidex PA(copyright), Johnson and Johnson). The minimum effective PAA concentration for high-level disinfection at 25 minutes (min) and 20xc2x0 C. is 0.05%w/v (500 ppm) in the presence of 1.0%w/v H2O2 (Peract(trademark) 20).
Medical devices such as thermometers and hydrotherapy tanks are also classified as semicritical, but they require intermediate-level rather than high-level disinfection prior to reuse. Intermediate-level disinfection inactivates M. tuberculosis, vegetative bacteria, most viruses and most fungi, but does not necessarily kill bacterial spores. A common intermediate-level disinfectant is Cavicide(copyright) (Metrex Research Corp.), which contains 0.28%w/v diisobutylphenoxyethoxyethyl dimethyl benzyl ammonium chloride, (a so-called super quat) and 17.2%w/v isopropyl alcohol.
Noncritical medical devices, for example, stethoscopes, tabletops, bedpans, etc., touch intact skin and require low-level disinfection prior to reuse. Low-level disinfection can kill most bacteria, some viruses, and some fungi, but it cannot be relied upon to kill resistant microorganisms such as tubercle bacilli or bacterial spores. Contact lenses are included in the class of devices which require low-level disinfection prior to reuse. Common low-level disinfectants for contact lens disinfection include acidic 3.0%w/v H2O2 and 1-10 ppm solutions of polymeric antimicrobial biguanides or quaternary ammonium compounds (e.g., 1 ppm polyhexamethylene biguanide in Complete(copyright) (Allergan Pharmaceuticals, Inc.) or 10 ppm Polyquad(trademark) polyquaternary ammonium compound in Optifree(copyright) (Alcon, Inc.).
Standards for sterilization and low, intermediate and high-level disinfection have been concurrently established. These standards are based upon the known or possible risk of contamination of a particular medical device by a particular microorganism, the pathogenic nature of the organism and other principles in infection control. They typically require demonstration of sterilization and/or disinfection efficacy against a particular panel of test organisms, which collectively represent the known or possible contamination and infection risks. The test panels and criteria are different for low, intermediate or high-level disinfection. It is also generally accepted that a high-level disinfectant will meet the disinfection efficacy standards of intermediate- and low-level disinfection as well. It is universally accepted that low-level disinfection performance cannot predict intermediate- or high-level disinfection performance. In fact, it is assumed prior to testing that a low-level disinfectant cannot achieve a higher level disinfection standard. Additionally, other factors such as device compatibility with the disinfection system must also be considered. For example, no high-level disinfecting agent can be used for contact lens low-level disinfection because of the inherent incompatibility of the chemistry of the high-level disinfectants with either the contact lens, contact lens case or eyes with respect to neutralization requirements prior to wearing the lenses. Complicating this issue further is the introduction of cleaning agents into the overall disinfection care system.
Cleaning is the removal of all foreign material, including organic soil such as blood, feces, respiratory secretions, etc., from objects. It has been reported that failure to remove foreign material from a medical device such as an endoscope before a disinfection or sterilization process is likely to render the process ineffective. (Rutala, W A, APIC Guideline for Selection and Use of Disinfectants, Am J Infect Control, August 1996; Vol. 24,4:313-342). The presence of organic material or soil may contribute to the failure of disinfection by harboring embedded microbes and preventing the penetration of the germicide. Additionally, some disinfectants are inactivated by organic material (Martin, M A, Reichelderfer, M, APIC Guideline for Infection Prevention and Control in Flexible Endoscopy, Am J Infect Control, 1994;22:19-38). Major reasons reported for transmission of nosocomial infections related to endoscopes were inadequate cleaning, improper selection of a high-level disinfectant, or failure to follow recommended cleaning and high-level disinfecting procedures (Spach, D H, et. al., Transmission of Infection by Gastrointestinal Endoscopy and Bronchoscopy, Ann Intern Med 1993;118:117-28.). Current medical industry recommendations for the reprocessing of semicritical medical devices such as endoscopes call for meticulous physical cleaning to precede high-level disinfection and sterilization procedures (Simmons, B P, Guideline for Hospital Environmental Control, Am J Infect Control 1983;11:97-115; Rutala, W A et. al., Disinfection Practices for Endoscopes and Other Semicritical Items, Infect Control Hosp Epidemiol, 1991;12:282-8). An additional problem is that coagulated blood can build up and lead to blocking of the various channels of a flexible fiberoptic endoscope. It is difficult to effectively remove organic material such as blood, mucus and feces from the narrow channels and exterior sections of flexible fiberoptic endoscopes. Ineffective removal of deposits results in costly routine maintenance to prevent blockages.
Current recommendations for cleaning and high-level disinfecting of semicritical medical devices such as flexible endoscopes and other similar instruments have been published. In general, endoscope disinfection involves six steps: (1) cleanxe2x80x94mechanically clean external surfaces, ports and internal channels with water and a detergent or enzymatic detergent; (2) rinsexe2x80x94rinse and drain channels with water; (3) disinfectxe2x80x94immerse endoscope in high-level disinfectant, perfuse disinfectant into suction and biopsy channel and air and water channel and expose for at least 20 min; (4) rinsexe2x80x94the endoscope and channels should be rinsed with sterile water; if this is not feasible use tap water followed with an alcohol rinse; (5) dryxe2x80x94the insertion tube and inner channels should be dried by forced air after disinfection and before storage; and (6) storexe2x80x94the endoscope should be stored in a way that prevents recontamination (Martin, M A, Reichelderfer, M, APIC Guideline for Infection Prevention and Control in Flexible Endoscopy, Am J Infect Control, 1994;22:19-38). Cleaning of endoscopes should be performed promptly after use to prevent drying of soils. Additionally, before cleaning, all endoscope channels should be irrigated with copious amounts of detergent and tap water to soften, moisten, and dilute organic debris.
Liquid enzymatic detergents used with semicritical medical devices are known also as enzymatic presoak and cleaning solutions. They are designed to be diluted with water at between xc2xd and 1 ounce per gallon of water prior to use and it is recommended they be used to presoak medical devices for between a few and 10 min or more. Users typically have the option to prepare the solution daily or more frequently if the solution is visibly soiled. Thus, current enzymatic detergents are reused over the course of one day. Soil antiredeposition agents are added to some formulas to facilitate solution reuse by preventing the redeposition of previously solubilized soils onto the next device placed into the cleaning solution.
High-level disinfecting solutions are also typically designed for a reuse option, depending upon the medical device. For example, a glutaraldehyde high-level disinfecting solution for endoscope reprocessing may be reused for as long as 28-30 days, while kidney dialyzers are disinfected with single-use solutions. The principle reason for reusing a solution is economic, as the practice itself provides the opportunity for adding to the risk of transmission of infection.
Thus, current medical device industry practices for semicritical medical devices such as endoscopes involve separate short cleaning and disinfecting steps and times, and reusable solutions. Longer soak cleaning or disinfecting times and single-use solutions would for the most part be impractical and uneconomical in the current environment.
Kidney dialyzers pose an additional problem in high level disinfecting in that the materials utilized require particular performance criteria of the cleaning and disinfection solutions. Types of dialyzers include: (1) coil, which incorporates a membrane in the form of a flattened tube wound around a central, rigid cylinder core, with a supporting mesh between adjacent portions of the membranes; (2) parallel plate, which incorporates a membrane in tubular or sheet form supported by plates in a sandwiched configuration; and (3) hollow-fiber, which incorporates the semipermeable membrane in the form of the walls of very small fibers having a microscopic channel running through them. Most parallel plate and hollow-fiber membranes are made from cellulose acetate, cellulose triacetate, regenerated cellulose, cuprophan or polysulfone. The semipermeable membranes used in dialyzers have large areas and high porosities, and after use become coated with blood proteins and other organic and cellular material. Dialysis fibers are also often clotted with blood cells, proteins and other debris. As a result, the membrane of a used dialyzer has a reduced capacity for dialysis and is highly susceptible to microbial growth. Effective killing of microorganisms on such a used membrane for the purpose of reusing the dialyzer is difficult to accomplish without damaging the membrane. When initially introduced, dialyzers were one-use devices. Since 1980, dialyzer reuse has risen dramatically in order to reduce the overall cost to the patient and the health care delivery system. Hemodialyzers, reprocessed in conformance with the Association for the Advancement of Medical Instrumentation (AAMI) specific guidelines and performance tests, have an average use number, that is, the number of times a particular hemodialyzer has been used in patient treatment. This number has been increasing over the years, from a United States average of 10 reuses in 1986 to 15 reuses in 1996. The cost benefits achieved by reprocessing are significant. For example, a new dialyzer costs about $20-30. With reprocessing, a dialyzer can be used between 5-20 times without substantial loss of efficacy. The cost of reprocessing is approximately $6.60-7.72 per unit, including reprocessing solutions. The cost per reuse for reprocessing solutions is $0.99-1.14 (average $1.08). The amortized dialyzer cost per reuse is $1.35-2.00, based upon an average reuse of 15 times. Additionally, the cost per reuse for dialyzer hazardous medical waste disposal is $0.50-0.55, reuse technician labor costs are $14/hr, and the associated labor cost of manual cleaning/dislodging clots is $0.23. Accordingly, with reprocessing, the dialyzer cost per treatment is conservatively less than about $10, as opposed to $30 if a new dialyzer were used for each treatment. A typical patient receives approximately 156 treatments per year. In 1998 in the United States alone there were approximately 280,000 patients on hemodialysis, and about 86% of hemodialysis centers have a dialyzer reuse program. Therefore, there are about 35,060,480 reuses in the United States (280,000xc3x970.86xc3x97(156xe2x88x92156/15)). The U.S. market for reprocessing solutions in 1998 is estimated to be $34.7-40.0 million. The number of patients on dialysis in the United States is growing at the rate of 7% per year. Additionally, the dialyzer reuse incidence of 86% in 1998 is expected to grow 2% per year to essentially 100% reuse by the year 2005. Utilizing a 3% rate of product price inflation, the United States market for reprocessing solutions is expected to be $83 million by the year 2005. Worldwide, the market for current generation reprocessing solutions is expected to be 1.5 times the United States market, or $125 million by the year 2005. The worldwide market has the potential to be much larger, as the prevalence rates of people on dialysis are expected to be greater than 1000 persons per million population in the United States, Japan and some European countries by the year 2000. Conceivably, 5 million people or more could be on dialysis worldwide if United States medical practices were fully adopted. This translates to a potential reprocessing solution market of $793 million in current dollars, based upon 145 solution uses per year per patient at $1.09 current cost per solution use.
In addition to cost savings with dialyzer reuse, there are health advantages. Researchers have determined that reused dialyzers significantly mitigate patients"" xe2x80x9cnew dialyzerxe2x80x9d symptoms as well as immune reactions that often occur. The inherent clinical advantage of reused dialyzers has been attributed to both the reduction in trace contaminants such as ethylene oxide sterilant, and to the masking of immune reaction sites located on the membrane surface by protein deposits.
Dialyzer reprocessing involves three basic steps: (1) cleaning, (2) dialysis efficacy confirmation, and (3) high-level disinfecting involving soak times long enough to achieve sterilization. The cleaning step involves removing residual blood, organic and cellular material from the blood side and removing dialysate from the dialysate side of the semipermeable membrane. A number of cleaning solutions are known, including sodium hypochlorite bleach, PAA and H2O2. Purified water has also been used for cleaning. The cleaning solution must be rinsed from the dialyzer, typically with water.
Sodium hypochlorite bleach at a concentration of 0.5-1.0%w/v for 3 min exposure is utilized for cleaning. However, significant decreases in patient urea and creatinine clearance have been observed with high-flux polysulfone (F80B) dialyzers reprocessed with formaldehyde and bleach (Murthy et. al., Effect of Formaldehyde/Bleach Reprocessing on In Vivo Performances of High-Efficiency Cellulose and High-Flux Polysulfone Dialyzers. J Am Soc Nephrol:464-472, 1997). Also, Kaplan and colleagues observed up to 20 g blood protein and specifically 15 g albumin loss into the dialysate per treatment with bleach-reprocessed, high-flux polysulfone (F80) dialyzers. Elimination of bleach from the reprocessing protocol led to a significant increase in serum albumin levels. (Kaplan et. al., Dialysate Protein Losses With Bleach Processed Polysulfone Dialyzers. Kidney Int 47;573-578, 1995.) It is believed that reprocessing certain polysulfone dialyzers with bleach somehow alters membrane structure. Loss of the usual immune protection achieved with reused dialyzers has been shown to occur when sodium hypochlorite, particularly at elevated concentrations, is used for reprocessing, resulting in complement activation and neutropenia restored to near original levels. The problems associated with utilizing bleach in the reprocessing protocol have widespread ramifications; in the U.S. as of 1996, 42% of all patients were utilizing high-flux dialysis and 78% of those were utilizing polysulfone dialyzer membranes. Finally, while not reported within the kidney dialysis industry, it is known that chlorine bleach solution has a tendency to form so-called haloforms with organic compounds. These compounds are considered to be carcinogenic and are therefore also hazardous from the health perspective. In this context, it was recently reported that dialysis patients had an increase in cancer of 15% as compared to the general population (The Lancet, 354, 93-99, 1999).
Dialyzers reprocessed with H2O2-containing solutions have a significant reduction in ultrafiltration rate, indicating the presence of hydrolytically resistive protein deposits resistive to removal by H2O2. In addition, while H2O2-containing solutions are useful in that they react vigorously with hemoglobin, can be effective in dissolving some clots in dialyzer headers and blood channels, and can restore dialyzer fiber bundle volume in some cases, elevated concentrations of H2O2 can rapidly generate gaseous oxygen reaction products, as evidenced by the reported bursting of noncompliant membrane capillary fibers. PAA reacts similarly with protein deposits, as PAA contains an equilibrium mixture of H2O2, PAA and acetic acid. Thus, PAA will not remove protein deposits but can be effective in dissolving some clots.
Lastly, water used in the reprocessing cleaning step is generally ineffective in removing protein deposits or bound clots, as is the case with formaldehyde and glutaraldehyde.
The use of citric acid in connection with the cleaning of dialysis machines has been disclosed in a number of patents. Tell et al., U.S. Pat. No. 4,690,772, discloses a sterilizing and cleaning solution comprising sodium chlorite, citric acid and a sodium bicarbonate buffer. U.S. Pat. No. 5,480,565 to Levin discloses a method for reprocessing dialyzer cartridges used with kidney dialysis machines. The method involves filling the blood and dialysate compartments of the dialyzer with an aqueous solution containing citric acid at a concentration of about 1.0-5.0%w/v and then subjecting the dialyzer to an elevated temperature above 90xc2x0 C. and below 100xc2x0 C. for a period of at least 15 hours (h). It is known, however, that citric acid is incapable of removing bound protein deposits from polymer surfaces at these temperatures. Moreover, the sodium chlorite solutions in the ""772 patent have the capacity to crosslink proteins in surface deposits, making them even more resistant to removal. Also, the heat utilized in the ""565 patent will further denature proteins and possibly create more deposits, as well as deposits which are more resistant to removal.
The efficacy confirmation step for dialyzer reprocessing involves confirming that membrane integrity and performance is substantially equivalent to that of a new dialyzer. Specifically, with respect to membrane performance, when the measured fiber bundle volume (FBV) of the membrane drops by 20%, the dialyzer is no longer reused.
The disinfection step involves subjecting the dialyzer to high level disinfection with a process or chemical disinfecting agent. Chemical disinfecting agents such as formaldehyde, glutaraldehyde or an equilibrium mixture of PAA, H2O2 and acetic acid are typically employed. In the United States in 1996, 36% of dialysis centers used formaldehyde, 54% used PAA, 7% used glutaraldehyde and 3% used heat to disinfect and sterilize. A commonly used glutaraldehyde solution is Diacide(copyright) (Gulfstream Corp.) a 26%w/v concentrate of acidic glutaraldehyde which is activated with alkali just prior to use and then diluted with water to a final concentration of 0.8%w/v. In 1998, the most commonly used PAA-based product was Renalin(copyright) Dialyzer Reprocessing Concentrate (Renal Systems Division, Minntech Corp). Renalin(copyright) is a concentrated solution of 4%w/v PAA and 24%w/v H2O2, designed to be diluted to a 3.5%w/v concentration in water, yielding a final concentration of 0.14%w/v (1400 ppm) PAA and about 0.84%w/v (8400 ppm) H2O2.
The chemical disinfecting agent must be able to be rinsed out of the dialyzer to below toxic levels, with a rinse-out period established for the particular agent. Typically, for glutaraldehyde disinfectants, 1 liter of isotonic sterile saline is perfused through the dialyzer fibers prior to dialyzer use, with sterile purified water additionally used to rinse the dialysate chamber. Moreover, since the dialyzer is connected to the vascular system during use, any residual chemical entity which may be reversibly bound to the semipermeable membrane and which may desorb from the dialyzer following the rinse should be non-immunogenic, i.e., it should not provoke an immune response.
PAA compositions for cleaning, or cleaning and low level disinfecting, have been disclosed in several publications. UK patent application GB 2129458 A filed Oct. 24, 1983 by Tatin and assigned to PCUK Produits Chimiques Ugine Kuhlmann discloses single-use washing compositions comprising an alkali metal perborate and an activator for decomposing the perborate to PAA, the activator selected from cyanamide and metal salts thereof, and a proteolytic enzyme obtained from a strain of bacillus. The perborate is preferably sodium perborate, used at a standard concentration for a washing powder of 15%w/v or 1 g/l of bath and produces a H2O2 concentration of 0.0220%w/v (220 ppm). The quantity of cyanamide activator is between 2-8%w/w of the total washing agent, corresponding to 0.0133-0.0533%w/v (133-533 ppm). The concentration of PAA produced by the aforementioned mixture of 220 ppm H2O2 and 533 ppm activator is not represented, but cannot exceed 220 ppm. These concentrations of PAA and remaining H2O2 (if any) are well below the minimum effective concentration of 500 ppm PAA and 1.0%w/v H2O2 to achieve high level disinfection in 25 min and sterilization in a longer time interval.
Gray, U.S. Pat. No. 3,714,050 discloses a dry single-use composition containing sodium perborate, a proteolytic enzyme and MgSO4 for removing stains from fabrics. In the preferred form the composition contains a perborate activator which produces a percarboxylic acid. A preferred perborate range is one which provides a concentration of xe2x80x9cperxe2x80x9d compound (e.g., a compound with or containing the chemical structure Rxe2x80x94Oxe2x80x94Oxe2x80x94R1, wherein both R and R1 can be H or another chemical group such as an acetyl group or a metal ion or another inorganic or organic atom or chemical group) in the soaking water equivalent to about 5-200 ppm of available oxygen. These compositions thus provide a PAA and remaining H2O2 concentration (if any), which are well below the minimum effective concentration of 500 ppm PAA and 1.0%w/v H2O2 required to achieve high level disinfection in 25 min and sterilization in a longer time interval.
Sarot, U.S. Pat. No. 3,816,319 discloses a process for activating peroxide compounds in aqueous solutions used for washing and bleaching or for unspecified decontamination and disinfection and also solid single-use compositions containing both a peroxide compound and the activator. The process includes activating peroxide compounds selected from the group consisting of H2O2, sodium perborate and sodium percarbonate, with the activator selected from the group consisting of diacylated glyoxime and diacylated dialkylglyoxime. The solid compositions comprise either sodium perborate or sodium percarbonate and an activator selected from the group consisting of diacylated glyoxime or diacylated dialkylglyoxime. Laundry cleaning tests were carried out with washing powders containing either 2 g/l of sodium perborate or sodium percarbonate, proteolytic enzymes and diacetylated dimethylglyoxime at a concentration of 0.35-0.40 g/l. These compositions will produce H2O2 at a concentration of 440 ppm from the sodium perborate and a somewhat higher concentration of H2O2 from the sodium percarbonate. The concentration of PAA produced by the aforementioned mixture of H2O2 and 400 ppm glyoxime activator is not represented, but can be estimated to be on the order of 400 ppm or less. The concentrations of PAA and H2O2 (if any remains) are well below the minimum effective concentration of 500 ppm PAA in the presence of 1.0%w/v H2O2 required to achieve high level disinfection in 25 minutes and sterilization in a longer time interval.
Patents for compositions and methods for cleaning and disinfecting a variety of medical devices have also issued. Some of the following disclosed compositions and methods are commercially available.
Knepper, German Patent No. 2,130,833 issued Jan. 11, 1973, discloses cleaning and disinfecting compositions for medical devices, especially tubular suction devices, comprising a mixture of protein-degrading enzymes, quaternary ammonium base for disinfection and other known cleaning agents such as phosphates and nonionic builders. However, quaternary ammonium base disinfecting compounds are suitable only for low level disinfection when used alone, that is, without other disinfecting agents. Neither the level of disinfection nor the enzymes are specified, however, an extremely long exposure of 12-48 hours is claimed to achieve cleaning: Additional surfactants, metal corrosion inhibitors, chelating agents, buffers and soil redeposition inhibitors are not disclosed. The ""833 patent does not pertain to reusable cleaning and disinfecting solutions.
Huth, U.S. Pat. No. Re. 32,672 discloses a one step method for simultaneously cleaning and disinfecting contact lenses comprising contacting the lenses with a solution comprised of a disinfecting amount of peroxide and an effective amount of peroxide-active proteolytic enzyme for a time sufficient to remove substantially all protein accretions and to disinfect the lenses. The preferred peroxide is H2O2 in a preferred amount of 3%w/v, however, an amount of 10%w/v or more is also disclosed, limited only by the requirement that the enzyme retains proteolytic activity. A disinfecting amount of peroxide is defined as the amount that will reduce the microbial burden by one logarithm in three hours. The microbial burden and disinfection pertain solely to microorganisms contaminating contact lenses and the low-level disinfecting standards required by the Food and Drug Administration (FDA) for antimicrobial testing of contact lens disinfecting products. These low-level disinfection standards are based upon antimicrobial efficacy testing against particular panels of test organisms, the USP XXI Panel and the FDA xe2x80x9cSoft Lensxe2x80x9d Panel, both of which are representative of the types of organisms found specifically on contact lenses. Thus, disinfection in the ""672 patent does not pertain to the standards for intermediate- and high-level disinfection of other medical devices such as endoscopes and kidney dialysis devices, the latter of which requires high-level disinfection, nor does the it pertain to sterilization of medical devices. The ""672 patent discloses that the enzymes may be derived from any plant, animal or microbial source and may be acidic, neutral or alkaline. Additional surfactants or soil redeposition inhibitors are not disclosed. Corrosion inhibitors to prevent metal part or adhesive corrosion are not disclosed, as contact lenses do not contain metal parts or adhesives. Chelating agents are also not disclosed. The ""672 patent also does not pertain to reusable cleaning and disinfecting solutions.
Disch, U.S. Pat. No. 5,234,832 discloses a process for cleaning and disinfecting surfaces of heat and corrosion sensitive medical instruments with an aqueous cleaning and disinfecting solution. The process comprises, in successive steps, (a) contacting the surfaces to be cleaned and disinfected for about 1-15 min with the aqueous detergent and disinfectant solution at pH between 6-8 and a temperature of about 55xc2x0 C.-65xc2x0 C. and which contains (1) water having a hardness of 3-8 German hardness (Gh) units, (2) at least one low foaming nonionic surfactant (3) at least one proteolytic enzyme (4) at least one complexing agent (5) at least one aldehyde disinfectant selected from the group consisting of formaldehyde and aliphatic dialdehydes containing 2-8 carbon atoms; (b) rinsing the surfaces at least twice with water having a hardness of 3-8 Gh and at a temperature of about 55xc2x0 C.-65xc2x0 C. at least in the last rinse cycle; and (c) drying the surfaces with sterilized air at a temperature of about 40xc2x0 C.-60xc2x0 C. The addition of soil redeposition inhibitors is not disclosed, nor are specific metal corrosion inhibitors. Aliphatic dialdehydes utilized in the ""832 patent include glutaraldehyde, which is a commonly used high-level disinfectant for medical devices such as endoscopes. The ""832 patent utilizes proteolytic enzymes obtained from bacterial strains of the same type utilized in the ""672 patent. It is known, however, that bacterial proteolytic enzymes such as subtilisin retain little activity in the presence of glutaraldehyde at a concentration suitable for high-level disinfection, thus no functional cleaning would occur. The ""832 patent also does not pertain to reusable cleaning and disinfecting solutions.
Huth, U.S. Pat. No. 5,356,555 discloses a method for simultaneously cleaning and disinfecting a contact lens, comprising the steps of (1) forming a disinfecting solution comprising polyhexamethylene biguanide and other excipients, (2) providing an effective and efficacious amount of subtilisin A proteolytic enzyme, (3) combining the contact lens, the disinfection solution and the subtilisin A and (4) soaking the lens in the resulting solution for a period of time sufficient to clean and disinfect. Enzymes disclosed in the ""672 patent are also employed in the ""555 patent. Again, the microbial burden and disinfection pertain solely to microorganisms contaminating contact lenses and the low-level disinfection standards required by the FDA for antimicrobial testing of contact lens disinfection products. Surfactants are disclosed. The use of soil redeposition inhibitors is not taught; however, two of the most commonly used soil redeposition inhibitors, carboxymethylcellulose and hydroxypropylmethylcellulose, are disclosed. The ""555 patent teaches that carboxymethylcellulose and hydroxypropylmethylcellulose can be used in amounts to detoxify the active disinfecting agent. Again, corrosion inhibitors to prevent metal part or adhesive corrosion are not disclosed as contact lenses do not contain metal parts or adhesives. The ""555 patent also does not pertain to reusable cleaning and disinfecting solutions.
Beerstecher, U.S. Pat. No. 5,571,488 discloses an apparatus which utilizes an improved method to enable an optimum hygienic preparation of medical and dental instruments. Instruments are placed into a chamber that can be closed pressure-tight and in which the following steps can be automatically sequenced in a preselected process. The steps of the method comprise (a) cleaning the exterior surfaces of the instrument as well as potentially any media channels with a high-energy water jet directed onto the instruments, first with cold water and subsequently with pre-heated water, (b) intensive after-cleaning and disinfection of the exterior surfaces and, potentially, of the media channels as well as of the moving internal parts and their bearings by blowing off and out with a water stream at a temperature between approximately 60xc2x0 C.-100xc2x0 C. (c) caring for the moving internal parts and their bearings of the instrument by injecting a metered quantity of lubricant (d) sterilizing the instruments inside and out with saturated water steam at a temperature of, preferably, 130xc2x0 C. and then (e) drying and cooling the instruments with a coolant, preferably compressed air. The ""488 patent does not pertain to a chemical-based system employing cleaning and disinfecting agents, nor does it pertain to reusable cleaning and disinfecting solutions.
None of the above cleaning and disinfecting systems provides for a simple and easy to use, functional, single use or reusable system for simultaneous cleaning and decontaminating devices such as medical devices (e.g., endoscopes). None of the above systems provide for a simple, functional single use or reusable system for simultaneous cleaning and high-level disinfecting or sterilizing a kidney dialyzer. Thus, there is a need for improved compositions and methods for such applications.
The invention is directed to a composition to simultaneously clean and decontaminate (i.e., sterilize or high-level disinfect) a device, for example a medical devise such as an endoscope or a kidney dialyzer. The composition is a per-compound oxidant, such as hydrogen peroxide (H2O2) and/or peracetic acid (PAA) and an enzyme. The enzyme may be proteolytic, human or non-human, and may be active at an acid, alkaline or neutral pH. Examples of enzymes are include subtilisin, trypsin, chymotrypsin and pepsin. Preferred concentrations are 0.5-50%w/w H2O2, 0.05-5%w/w PAA and 0.00001-10 Anson Units (A.U.)/ml enzyme. The composition may also include a corrosion inhibitor to prevent corrosion of a metal device, a chelator, a buffer, a dye or combinations of these. The composition may be reused to simultaneously clean and decontaminate a plurality of devices and the composition may be periodically recharged with enzyme.
The invention is also directed to a method to simultaneously clean and decontaminate a device after removing loosely adhering soil from the device, for example, by manually removing soil with a cloth and/or by rinsing with water or with an enzyme or non-enzyme detergent. The device is then contacted, for example by immersing the device in the composition, with the composition of the invention as described above. The composition can then be removed from the device, for example, by rinsing with sterile water or saline. These steps can be performed on a plurality of devices while reusing the same composition. The device can rinsed with alcohol, dried and stored to prevent recontamination.
A preferred composition includes about 0.05-5%w/w PAA, about 0.001-2.0 A.U./ml protease with the protease in solution concentrate form to be diluted in the PAA solution, and about 0.05-5.3%w/v chelator, with the composition having a pH between 5-9. Another particularly preferred composition includes about 0.10-1.0%w/v of a corrosion inhibitor in the previous composition and the composition having a pH between 1-5. Particularly preferred methods include contacting one or more medical devices with these compositions.
A particularly preferred composition to simultaneously clean and decontaminate a kidney dialyzer is a mixture of about 0.5-1.5%w/w H2O2, about 0.05-3.0% w/w PAA, and about 0.00001-0.10 A.U./ml human pepsin, with the composition having a pH between 1-6. Another particularly preferred composition to simultaneously clean and decontaminate a kidney dialyzer is a mixture of about 0.5-1.5%w/w H2O2, about 0.05-3.0%w/w PAA and about 0.00001-0.10 A.U./ml human trypsin, with the composition having a pH between 6-9. In a particularly preferred method, the ends of the fiber bundles of the dialyzer are contacted with either of the previously described compositions.
It will be appreciated that the disclosed simultaneous cleaning and decontaminating compositions and methods of the invention have a wide array of applications. These and other advantages of the invention will be further understood with reference to the following drawing, detailed description and examples.